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Full-Text Articles in Pharmacy and Pharmaceutical Sciences
Arachidonic Acid Activates A Proton Current In The Rat Glutamate Transporter Eaat4, Anastassios V. Tzingounis, Chien-Liang Lin, Jeffrey D. Rothstein, Michael Kavanaugh
Arachidonic Acid Activates A Proton Current In The Rat Glutamate Transporter Eaat4, Anastassios V. Tzingounis, Chien-Liang Lin, Jeffrey D. Rothstein, Michael Kavanaugh
Biomedical and Pharmaceutical Sciences Faculty Publications
The excitatory amino acid transporter EAAT4 is expressed predominantly in Purkinje neurons in the rat cerebellum (1-3), and it participates in postsynaptic reuptake of glutamate released at the climbing fiber synapse (4). Transporter-mediated currents in Purkinje neurons are increased more than 3-fold by arachidonic acid, a second messenger that is liberated following depolarization-induced Ca2+ activation of phospholipase A2 (5). In this study we demonstrate that application of arachidonic acid to oocytes expressing rat EAAT4 increased glutamate-induced currents to a similar extent. However, arachidonic acid did not cause an increase in the rate …
Macroscopic And Microscopic Properties Of A Cloned Glutamate Transporter/Chloride Channel, Jacques I. Wadiche, Michael Kavanaugh
Macroscopic And Microscopic Properties Of A Cloned Glutamate Transporter/Chloride Channel, Jacques I. Wadiche, Michael Kavanaugh
Biomedical and Pharmaceutical Sciences Faculty Publications
The behavior of a Cl− channel associated with a glutamate transporter was studied using intracellular and patch recording techniques in Xenopus oocytes injected with human EAAT1 cRNA. Channels could be activated by application of glutamate to either face of excised membrane patches. The channel exhibited strong selectivity for amphipathic anions and had a minimum pore diameter of ∼5Å. Glutamate flux exhibited a much greater temperature dependence than Cl− flux. Stationary and nonstationary noise analysis was consistent with a sub-femtosiemen Cl− conductance and a maximum channelPo ≪ 1. The glutamate binding rate was similar to estimates …
Neurotransmitter Transport: Models In Flux, Michael Kavanaugh
Neurotransmitter Transport: Models In Flux, Michael Kavanaugh
Biomedical and Pharmaceutical Sciences Faculty Publications
Physiologists say that ions and neutral solutes can cross biological membranes via “transporters” and “channels.” We tend to think about the difference between transporters and channels in terms of gating mechanisms. Ion channels exhibit a wide range of selectivity properties and permeation rates, but their gating at the most basic level can be thought of in terms of a single barrier or gate acting as a switch. When the gate is closed, ions can’t permeate; when the gate is opened, a permeation pathway for ions allows flux, often at very high rates (up to 108/sec). Transporters and ion …
Gp120 Envelope Glycoproteins Of Human Immunodeficiency Viruses Competitively Antagonize Signaling By Coreceptors Cxcr4 And Ccr5, Navid Madani, Susan L. Kozak, Michael Kavanaugh, David Kabat
Gp120 Envelope Glycoproteins Of Human Immunodeficiency Viruses Competitively Antagonize Signaling By Coreceptors Cxcr4 And Ccr5, Navid Madani, Susan L. Kozak, Michael Kavanaugh, David Kabat
Biomedical and Pharmaceutical Sciences Faculty Publications
Signal transductions by the dual-function CXCR4 and CCR5 chemokine receptors/HIV type 1 (HIV-1) coreceptors were electrophysiologically monitored in Xenopus laevis oocytes that also coexpressed the viral receptor CD4 and a G protein-coupled inward-rectifying K+ channel (Kir 3.1). Large Kir 3.1-dependent currents generated in response to the corresponding chemokines (SDF-1α for CXCR4 and MIP-1α; MIP-1β and RANTES for CCR5) were blocked by pertussis toxin, suggesting involvement of inhibitory guanine nucleotide-binding proteins. Prolonged exposures to chemokines caused substantial but incomplete desensitization of responses with time constants of 5–7 min and recovery time constants of 12–19 min. CXCR4 and CCR5 exhibited heterologous …
Cysteine Scanning Of The Surroundings Of An Alkali-Ion Binding Site Of The Glutamate Transporter Glt-1 Reveals A Conformationally Sensitive Residue, Ruth Zarbiv, Myriam Grunewald, Michael Kavanaugh, Baruch I. Kanner
Cysteine Scanning Of The Surroundings Of An Alkali-Ion Binding Site Of The Glutamate Transporter Glt-1 Reveals A Conformationally Sensitive Residue, Ruth Zarbiv, Myriam Grunewald, Michael Kavanaugh, Baruch I. Kanner
Biomedical and Pharmaceutical Sciences Faculty Publications
Glutamate transporters remove this transmitter from the extracellular space by cotransport with three sodium ions and a proton. The cycle is completed by translocation of a potassium ion in the opposite direction. Recently we have identified two adjacent amino acid residues of the glutamate transporter GLT-1 that influence potassium coupling. Using the scanning cysteine accessibility method we have now explored the highly conserved region surrounding them. Replacement of each of the five consecutive residues 396–400 by cysteine abolished transport activity but at several other positions the substitution is tolerated. One residue, tyrosine 403, was identified where cysteine substitution renders the …
Molecular Determinant Of Ion Selectivity Of A (Na+ + K+)-Coupled Rat Brain Glutamate Transporter, Yumin Zhang, Annie Bendahan, Ruth Zarbiv, Michael Kavanaugh, Baruch I. Kanner
Molecular Determinant Of Ion Selectivity Of A (Na+ + K+)-Coupled Rat Brain Glutamate Transporter, Yumin Zhang, Annie Bendahan, Ruth Zarbiv, Michael Kavanaugh, Baruch I. Kanner
Biomedical and Pharmaceutical Sciences Faculty Publications
Glutamate transporters remove this neurotransmitter from the synaptic cleft by a two-stage electrogenic process, in which glutamate is first cotransported with three sodium ions and a proton. Subsequently, the cycle is completed by translocation of a potassium ion in the opposite direction. Recently, we have identified an amino acid residue of the glutamate transporter GLT-1 (Glu-404) that influences potassium coupling. We have now analyzed the effect of seven other amino acid residues in the highly conserved region surrounding this site. One of these residues, Tyr-403, also proved important for potassium coupling, because mutation to Phe (Y403F) resulted in an electroneutral …
Excitatory Amino Acid Transporters Of The Salamander Retina: Identification, Localization, And Function, Scott Eliasof, Jeffrey L. Arriza, Barbara H. Leighton, Michael Kavanaugh, Susan G. Amara
Excitatory Amino Acid Transporters Of The Salamander Retina: Identification, Localization, And Function, Scott Eliasof, Jeffrey L. Arriza, Barbara H. Leighton, Michael Kavanaugh, Susan G. Amara
Biomedical and Pharmaceutical Sciences Faculty Publications
The rapid re-uptake of extracellular glutamate mediated by a family of high-affinity glutamate transporter proteins is essential to continued glutamatergic signaling and neuronal viability, but the contributions of individual transporter subtypes toward cellular physiology are poorly understood. Because the physiology of glutamate transport in the salamander retina has been well described, we have examined the expression and function of glutamate transporter subtypes in this preparation. cDNAs encoding five distinct salamander excitatory amino acid transporter (sEAAT) subtypes were isolated, and their molecular properties and distributions of expression were compared. We report evidence that at least four distinct sEAAT subtypes are expressed …